New therapy for glaucoma and optic neuritis using Dock3

2012 Fiscal Year Final Research Report

• Project/Area Number: 23792024
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: 公益財団法人東京都医学総合研究所 (2012); Tokyo Metropolitan Organization for Medical Research (2011)
• Principal Investigator: KIMURA Atsuko 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研究員 (60569143)
• Project Period (FY): 2011 – 2012
• Keywords: Dock3 / 緑内障 / 視神経炎

Research Abstract

We previously showed that neuron-specific Dock3, a new member of the guanine nucleotide exchange factors for the small GTPase Rac1, induces axonal outgrowth in retinal ganglion cells (RGCs). In this study, we found that Dock3 protects RGCs from both glutamate neurotoxicity and oxidative stress. We also demonstrated that Dock3 overexpression prevents glaucomatous retinal degeneration in GLAST deficient mice, a model of normal tension glaucoma.

Research Products

• [Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury (2013)
  • Author(s): Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T
  • Journal Title: Cell Death and Differentiation Volume: 20(2) Pages: 270-280
  • DOI: doi:10.1038/cdd.2012.122.
  • Peer Reviewed
• [Journal Article] ASK1-p38 経路の阻害は視神経外傷後の神経細胞死を抑制する (2013)
  • Author(s): 香留 崇、行方和彦、郭 暁麗、仙波賢太郎、橘高大二、川村和人、木村敦子、原田知加子、一條秀憲、三田村佳典、原田高幸
  • Journal Title: 日眼会誌 Volume: 117(2) Pages: 161
• [Journal Article] Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG (2012)
  • Author(s): Namekata, K., Watanabe, H., Guo, X., Kittaka, D., Kawamura, K., Kimura, A., Harada, C. and Harada, T
  • Journal Title: Genes to Cells Volume: 17(8) Pages: 688-697
  • DOI: doi:10.1111/j.1365-2443.2012.01616.x.
  • Peer Reviewed
• [Journal Article] Dock3 stimulates axonal outgrowth via GSK-3β-mediated microtubule assembly (2012)
  • Author(s): Namekata, K., Harada, C., Guo, X., Kimura, A., Kittaka, D., Watanabe, H. and Harada, T
  • Journal Title: Journal of Neuroscience Volume: 32(1) Pages: 264-274
  • DOI: doi:10.1523/JNEUROSCI.4884-11.2012.
  • Peer Reviewed
• [Journal Article] Dock3はグリコーゲン合成酵素キナーゼ-3β (GSK-3β)による微小管重合を介して軸索伸長を促進する (2012)
  • Author(s): 行方和彦、原田知加子、郭 暁麗、木村敦子、橘高大二、渡邉快記、原田高幸
  • Journal Title: 日眼会誌 Volume: 116(5) Pages: 527
• [Journal Article] Glia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration (2011)
  • Author(s): Harada, C., Guo, X., Namekata, K., Kimura, A., Nakamura, K., Tanaka, K., Parada, L.F., and Harada, T
  • Journal Title: Nature Communications Volume: 2 Pages: 189
  • DOI: doi:10.1038/ncomms1190.
  • Peer Reviewed
• [Journal Article] Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis (2011)
  • Author(s): Guo, X., Harada, C., Namekata, K., Kimura, A., Mitamura, Y., Yoshida, H., Matsumoto, Y., and Harada, T
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 52(5) Pages: 2696-2703
  • DOI: doi:10.1167/iovs.10-6015.
  • Peer Reviewed
• [Journal Article] Spermidine投与による実験的自己免疫性脳脊髄炎の軽症化 (2011)
  • Author(s): 郭 暁麗、原田知加子、行方和彦、木村敦子、三田村佳典、吉田 寛、松本 陽、原田高幸
  • Journal Title: 日眼会誌 Volume: 115(8) Pages: 729
• [Journal Article] 網膜の変性と再生過程におけるグリアおよび神経特異的なTrkBシグナルの機能解析 (2011)
  • Author(s): 原田知加子、郭 暁麗、行方和彦、木村敦子、中村和昭、田中光一、Luis F. Parada、原田高幸
  • Journal Title: 日眼会誌 Volume: 115(7) Pages: 637
• [Journal Article] TLR-ASK1-p38経路による神経炎症と脱髄症状の制御 (2011)
  • Author(s): 郭 暁麗、原田知加子、行方和彦、松沢 厚、Monsterrat Camps、Hong Ji、Dominique Swinnen、Catherine Jorand-Lebrun、Mathilde Muzerelle、Pierre-Alain Vitte、Thomas Ruckle、木村敦子、神山邦子、松本 陽、一條秀憲、原田高幸
  • Journal Title: 日眼会誌 Volume: 115(5) Pages: 485
• [Journal Article] Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma
  • Author(s): Namekata, K., Kimura, A., Kawamura, K., Guo, X., Harada, C., Tanaka, K. and Harada, T
  • Journal Title: Cell Death and Differentiation Volume: (in press)
  • Peer Reviewed
• [Presentation] The role of Dock3 in axon regeneration following optic nerve injury (2012)
  • Author(s): Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, Atsuko Kimura, Takayuki Harada
  • Organizer: XX International Congress of Eye Research (ISER 2012)
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-07-24
• [Presentation] Session "Macrophages and microglial regulation of ocular inflammation" ASK1 inhibition ameliorates optic neuritis by modulating glial innate immunity (2012)
  • Author(s): Xiaoli Guo, Chikako Harada, Kazuhiko Namekata, Atsuko Kimura, Takayuki Harada
  • Organizer: XX International Congress of Eye Research (ISER2012)
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-07-23
• [Presentation] ASK1 inhibition ameliorates optic neuritis by modulating glial innate immunity (2011)
  • Author(s): Xiaoli Guo, Chikako Harada, Kazuaki Nakamura, Atsuko Kimura, Hidenori Ichijo, Takayuki Harada
  • Organizer: The 26th Asia Pacific Academy of Ophthalmology (APAO) Congress
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2011-03-22